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This work presents the results of analysis of the final energy demand (Qk) for a single-family house in a pandemic situation and accompanying self-isolation of residents. It was assumed that the object of study is located in Bialystok (Poland). This analysis covers the impact of various factors such as specific periods of the active pandemic phase, the length of the inhabitants’ self-isolation period, the number of residents at home, and the type of energy source used in the building. Based on the results of computational experiments, a deterministic mathematical model of the relationship between these variables was developed, and the effects of the selected factors on the final energy demand were analyzed for the typical meteorological year (TMY) weather data. It turned out that the change in the length of the self-isolation period from 0 to 31 days caused an increase of Qk by about 6.5% for the analyzed building. When the number of inhabitants changed from 1 to 4, Qk increased by 34.7%. A change from 4 to 7 people causes an additional 26.7% increase in Qk. It was found that the structure of energy demand for this building operation during the period of inhabitants’ self-isolation also changed. With the increase in the length of the self-isolation period from 0 to 31 days, the electricity demand (Eel) increases by about 40–42%, while the demand for energy related to fuel consumption (Qg) decreases by about 7–10%. The article also presents an analysis of the impact of residents’ self-isolation on indoor air quality (IAQ) and thermal comfort. The simulation results showed that the use of variable air volume ventilation allows the CO2 concentration to be kept significantly below the limit value.

Analysis of the Impact of Self-Isolation of Residents during a Pandemic on Energy Demand and Indoor Air Quality in a Single-Family Building